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1.
Sci Total Environ ; 931: 172781, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38685433

ABSTRACT

Lead (Pb) is one of the most common heavy metal pollutants that possesses multi-organ toxicity. For decades, great efforts have been devoted to investigate the damage of Pb to kidney, liver, bone, blood cells and the central nervous system (CNS). For the common, dietary exposure is the main avenue of Pb, but our knowledge of Pb toxicity in gastrointestinal tract (GIT) remains quite insufficient. Importantly, emerging evidence has documented that gastrointestinal disorders affect other distal organs like brain and liver though gut-brain axis or gut-liver axis, respectively. This review focuses on the recent understanding of intestinal toxicity of Pb exposure, including structural and functional damages. We also review the influence and mechanism of intestinal toxicity on other distal organs, mainly concentrated on brain and liver. At last, we summarize the bioactive substances that reported to alleviate Pb toxicity, providing potential dietary intervention strategies to prevent or attenuate Pb toxicity.


Subject(s)
Environmental Pollutants , Lead , Lead/toxicity , Humans , Environmental Pollutants/toxicity , Intestines/drug effects , Liver/drug effects , Animals , Brain/drug effects
2.
Environ Res ; 251(Pt 2): 118752, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38513750

ABSTRACT

Human beings are routinely exposed to chronic and low dose of Bisphenols (BPs) due to their widely pervasiveness in the environment. BPs hold similar chemical structures to 17ß-estradiol (E2) and thyroid hormone, thus posing threats to human health by rendering the endocrine system dysfunctional. Among BPs, Bisphenol-A (BPA) is the best-known and extensively studied endocrine disrupting compound (EDC). BPA possesses multisystem toxicity, including reproductive toxicity, neurotoxicity, hepatoxicity and nephrotoxicity. Particularly, the central nervous system (CNS), especially the developing one, is vulnerable to BPA exposure. This review describes our current knowledge of BPA toxicity and the related molecular mechanisms, with an emphasis on the role of Wnt signaling in the related processes. We also discuss the role of oxidative stress, endocrine signaling and epigenetics in the regulation of Wnt signaling by BPA exposure. In summary, dysfunction of Wnt signaling plays a key role in BPA toxicity and thus can be a potential target to alleviate EDCs induced damage to organisms.


Subject(s)
Benzhydryl Compounds , Endocrine Disruptors , Phenols , Wnt Signaling Pathway , Phenols/toxicity , Benzhydryl Compounds/toxicity , Humans , Endocrine Disruptors/toxicity , Wnt Signaling Pathway/drug effects , Animals , Environmental Exposure/adverse effects , Environmental Pollutants/toxicity , Oxidative Stress/drug effects
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 314: 124199, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38555822

ABSTRACT

A series of "turn off" pH fluorescence probes with chalcone skeleton for basic system have been developed. The molecules emitted bright yellow fluorescence under acidic condition, resulting AIE coupled ESIPT characteristic and ICT process. What's more, the compounds exhibited excellent sensitivity and selectivity for detecting pH as a facile "On-Off" fluorescence probe, and the fluorescence of them were quenched with the ESIPT process interrupted under alkaline condition. Theoretical calculation for the related compounds also performed to verify the electron effect on photophysical properties and confirm the rational speculation on the mechanism.

4.
Toxicol Appl Pharmacol ; 482: 116776, 2024 01.
Article in English | MEDLINE | ID: mdl-38043803

ABSTRACT

Bisphenol A (BPA) has been implicated in cognitive impairment. Icariin is the main active ingredient extracted from Epimedium Herb with protective function of nervous system. However, the potential therapeutic effects of Icariin on spatial memory deficits induced by developmental BPA exposure in Sprague-Dawley rats have not been investigated. This study investigated the therapeutic effect of Icariin (10 mg/kg/day, from postnatal day (PND) 21 to PND 60 by gavage) on spatial memory deficits in rat induced by developmental BPA exposure (1 mg/kg/day, from embryonic to PND 60), demonstrating that Icariin can markedly improve spatial memory in BPA-exposed rat. Furthermore, intra-gastric administration of Icariin could attenuate abnormal hippocampal cell dispersion and loss, improved the dendritic spine density and Nissl bodies. Moreover, Icariin reversed BPA induced reduction of frequency of miniature excitatory postsynaptic currents(mEPSC) and decrease of Vesicular glutamate transporter 1(VGlut1). Collectively, Icariin could effectively rescue BPA-induced spatial memory impairment in male rats by preventing cell loss and reduction of dendritic spines in the hippocampus. In addition, we also found that VGlut1 is a critical target in the repair of BPA-induced spatial memory by Icariin. Thus, Icariin may be a promising therapeutic agent to attenuate BPA-induced spatial memory deficits.


Subject(s)
Flavonoids , Hippocampus , Phenols , Spatial Memory , Rats , Animals , Male , Rats, Sprague-Dawley , Benzhydryl Compounds/toxicity , Memory Disorders/chemically induced , Memory Disorders/prevention & control , Maze Learning
5.
J Nutr Biochem ; 125: 109556, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38151193

ABSTRACT

Kaempferol (Kam) is a flavonoid antioxidant found in fruits and vegetables, which was discovered as neuroprotective antioxidants. Lead (Pb), an environmental pollution, could induce learning and memory deficits. Nevertheless, little is known about the mechanisms underlying Kam actions in Pb-induced learning and memory deficits. In this study, we investigated the effects of Kam on Pb-induced cognitive deficits. Pb-exposed rats were treated with 50 mg/kg Kam from postnatal day (PND) 30 to PND 60. Then, Y-maze and Morris water maze have been used to detect the spatial memory in all groups of rats. Hematoxylin and eosin (HE) staining and Nissl staining were used to analyze the neuronal structure damages. The results found Kam treatment improved the learning and memory ability and alleviated hippocampal neuronal pathological damages. Besides, Kam could significantly reverse the synaptic transmission related protein expression including PSD95 and NMDAR2B. Further research found that Kam downregulated autophagy markers, P62, ATG5, Beclin1, and LC3-II. Furthermore, 3-MA, autophagy inhibitor, increased the levels of NMDAR2B and PSD95 in Pb-induced PC12 cells, indicating Kam alleviated Pb-induced neurotoxicity through inhibiting autophagy activation. Our results showed that Kam could ameliorate Pb-induced cognitive impairments and neuronal damages by decreasing Pb-induced excess autophagy accumulation.


Subject(s)
Cognitive Dysfunction , Lead , Rats , Animals , Lead/toxicity , Maze Learning , Kaempferols/pharmacology , Kaempferols/therapeutic use , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , Memory Disorders/chemically induced , Antioxidants/pharmacology , Autophagy
6.
Environ Res ; 236(Pt 1): 116717, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37495067

ABSTRACT

Bisphenol A (BPA), a widely used endocrine disruptor, has been implicated in cognitive impairment via epigenetic machinery. N6-methyl adenosine (m6A) has recently emerged as a new epigenetic factor that influences cognition, but the role of m6A in BPA induced cognitive deficits has not been explored yet. In this study, we found increased global m6A abundance accompanied with elevated expression of methyltransferase-like 3 (METTL3) in hippocampal neurons following BPA exposure. Inhibition of METTL3 activity by selective METTL3 inhibitor 2457 (STM) in cultured neurons abolished BPA induced m6A upregulation and abnormal synaptic transmission. Additionally, knockdown of METTL3 in hippocampus abrogated BPA induced learning and memory deficit in rats. Further study showed that m6A modification was enriched in mRNA of cholinergic receptor nicotinic alpha 4 subunit (Chrna4). Inhibition of METTL3 either by STM or shRNA restored BPA induced downregulation of Chrna4, suggesting that Chrna4 may be a potential target involved in BPA induced neurotoxicity that modified by m6A. Collectively, our findings demonstrated that METTL3 mediated m6A modification was involved in BPA induced cognitive deficit with Chrna4 as a potential target, which enriched our understanding of the role of epigenetics (RNA modifications) in BPA induced neurotoxicity and provided new insights into BPA or its substitutes induced damages in other organs.


Subject(s)
Benzhydryl Compounds , Methyltransferases , Rats , Animals , Methyltransferases/genetics , Methyltransferases/metabolism , Benzhydryl Compounds/toxicity , Phenols/toxicity
7.
Food Chem Toxicol ; 178: 113821, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37269892

ABSTRACT

Lead (Pb) is a pervasive heavy metal with multi-organ toxicity. However, the molecular mechanisms of Pb-induced neurotoxicity are not fully understood. The dynamics of N6-methylademine (m6A) is an emerging regulatory mechanism for gene expression, which is closely related to nervous system diseases. To elucidate the association between m6A modification and Pb-mediated neurotoxicity, primary hippocampal neurons exposed to 5 µM Pb for 48 h were used as the paradigm neurotoxic model in this study. According to the results, Pb exposure reprogrammed the transcription spectrum. Simultaneously, Pb exposure remodeled the transcriptome-wide distribution of m6A while disrupting the overall level of m6A in cellular transcripts. United analysis of MeRIP-Seq and RNA-Seq was applied to further identify the core genes whose expression levels are regulated by m6A in the process of lead-induced nerve injury. GO and KEGG analysis unveiled that the modified transcripts were overrepresented by the PI3K-AKT pathway. Mechanically, we elucidated the regulatory role of the methyltransferase like3 (METTL3) in the process of lead-induced neurotoxicity and the downregulation of the PI3K-AKT pathway. In conclusion, our novel findings shed new light on the functional roles of m6A modification in the expressional alternations of downstream transcripts caused by lead, providing an innovative molecular basis to explain Pb neurotoxicity.


Subject(s)
Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Proto-Oncogene Proteins c-akt/genetics , Phosphatidylinositol 3-Kinases/genetics , Lead/toxicity , Methyltransferases/metabolism , Neurons/metabolism
8.
Environ Sci Pollut Res Int ; 30(12): 33516-33523, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36480142

ABSTRACT

The presence of antibiotic resistance genes (ARGs) and heavy metal resistance genes (MRGs) in extracellular and intracellular DNA (eDNA and iDNA) has received considerable attention in recent years owing to the potential threat to human health and the ecosystem. As a result, we investigated six ARGs, three MRGs, and two mobile genetic elements (MGEs) in the municipal wastewater treatment plant (MWWTP) and its adjacent environments. Results revealed that the absolute abundances of eARGs and eMRGs were lower than iARGs and iMRGs in MWWTP. By contrast, eARGs and eMRGs were higher in river sediments. Among ARGs, aminoglycoside resistance genes (aadA) was the most abundant gene (3.13 × 102 to 2.31 × 106 copies/mL in iDNA; 1.27 × 103 to 7.23 × 105 copies/mL in eDNA) in MWWTP, while zntA gene (9.4 × 102 to 3.97 × 106 copies/mL in iDNA; 3.2 × 103 to 6 × 105 copies/mL in eDNA) was amongst the MRGs. Notably, intI1 was enriched and positively correlated with iDNA (tetA, sul1, blaCTX-M, ermB, and merA) and eDNA (blaCTX-M, ermB, and merA), demonstrating its function in the proliferation of resistance genes. This widespread distribution of ARGs, MRGs, and MGEs in MWWTP and its adjacent river sediments will help clarify the transmission routes within these environments and provide a theoretical basis for better monitoring and mitigation of such dissemination.


Subject(s)
Anti-Bacterial Agents , Water Purification , Humans , Anti-Bacterial Agents/pharmacology , Wastewater , Genes, Bacterial , Rivers , Ecosystem , Drug Resistance, Microbial/genetics
9.
Br J Radiol ; 94(1120): 20201356, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33571001

ABSTRACT

OBJECTIVES: To investigate the impact of total variation regularized expectation maximization (TVREM) reconstruction on the image quality of 68Ga-PSMA-11 PET/CT using phantom and patient data. METHODS: Images of a phantom with small hot sphere inserts and 20 prostate cancer patients were acquired with a digital PET/CT using list-mode and reconstructed with ordered subset expectation maximization (OSEM) and TVREM with seven penalisation factors between 0.01 and 0.42 for 2 and 3 minutes-per-bed (m/b) acquisition. The contrast recovery (CR) and background variability (BV) of the phantom, image noise of the liver, and SUVmax of the lesions were measured. Qualitative image quality was scored by two radiologists using a 5-point scale (1-poor, 5-excellent). RESULTS: The performance of CR, BV, and image noise, and the gain of SUVmax was higher for TVREM 2 m/b groups with the penalization of 0.07 to 0.28 compared to OSEM 3 m/b group (all p < 0.05). The image noise of OSEM 3 m/b group was equivalent to TVREM 2 and 3 m/b groups with a penalization of 0.14 and 0.07, while lesions' SUVmax increased 15 and 20%. The highest qualitative score was attained at the penalization of 0.21 (3.30 ± 0.66) for TVREM 2 m/b groups and the penalization 0.14 (3.80 ± 0.41) for 3 m/b group that equal to or greater than OSEM 3 m/b group (2.90 ± 0.45, p = 0.2 and p < 0.001). CONCLUSIONS: TVREM improves lesion contrast and reduces image noise, which allows shorter acquisition with preserved image quality for PSMA PET/CT. ADVANCES IN KNOWLEDGE: TVREM reconstruction with optimized penalization factors can generate higher quality PSMA-PET images for prostate cancer diagnosis.


Subject(s)
Edetic Acid/analogs & derivatives , Image Interpretation, Computer-Assisted/methods , Oligopeptides , Positron Emission Tomography Computed Tomography/methods , Prostatic Neoplasms/diagnostic imaging , Aged , Aged, 80 and over , Gallium Isotopes , Gallium Radioisotopes , Humans , Male , Middle Aged , Prostate/diagnostic imaging , Reproducibility of Results
10.
ACS Appl Bio Mater ; 4(6): 4946-4952, 2021 06 21.
Article in English | MEDLINE | ID: mdl-35007043

ABSTRACT

Oxygen-dependent photodynamic therapy (PDT) is hindered by the limited availability of endogenous oxygen in solid tumors and low tumor accumulation of photosensitizers. Herein, we developed a biocompatible cancer-targeted therapeutic nanosystem based on cRGD conjugated bovine serum albumin (CBSA) co-loaded with a photosensitizer (chlorin e6, Ce6) and a therapeutic protein (cytochrome c, Cytc) for synergistic photodynamic and protein therapy. The nanosystem (Ce6/Cytc@CBSA) can target αVß3 integrin overexpressed cancer cells to improve tumor accumulation due to incorporation of cRGD. In the intracellular environment, Ce6 is released to produce toxic singlet oxygen upon near-infrared irradiation. At the same time, the therapeutic protein, Cytc, can induce programmed cell death by activating the downstream caspase pathway. Most importantly, Cytc with the catalase-like activity accelerates O2 generation by decomposing excess H2O2 in cancer cells, thereby relieving the PDT-induced hypoxia to enhance therapeutic efficacy. Both in vitro and in vivo studies reveal the significantly improved antitumor effects of the combined photodynamic/protein therapy, indicating that Ce6/Cytc@CBSA shows great potential in synergetic cancer treatments.


Subject(s)
Chlorophyllides/administration & dosage , Cytochromes c/administration & dosage , Nanostructures/administration & dosage , Neoplasms/drug therapy , Photochemotherapy , Photosensitizing Agents/administration & dosage , Animals , Cell Line, Tumor , Cell Survival/drug effects , Chlorocebus aethiops , Chlorophyllides/pharmacokinetics , Cytochromes c/pharmacokinetics , Drug Synergism , Female , Mice, Inbred BALB C , Neoplasms/metabolism , Peptides, Cyclic/administration & dosage , Photosensitizing Agents/pharmacokinetics , Polyethylene Glycols/administration & dosage , Reactive Oxygen Species/metabolism , Serum Albumin, Bovine/administration & dosage , Tissue Distribution
11.
Adv Mater ; 32(17): e2000208, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32147886

ABSTRACT

Effective reversal of tumor immunosuppression is of critical importance in cancer therapy. A multifunctional delivery vector that can effectively deliver CRISPR-Cas9 plasmid for ß-catenin knockout to reverse tumor immunosuppression is constructed. The multi-functionalized delivery vector is decorated with aptamer-conjugated hyaluronic acid and peptide-conjugated hyaluronic acid to combine the tumor cell/nuclear targeting function of AS1411 with the cell penetrating/nuclear translocation function of TAT-NLS. Due to the significantly enhanced plasmid enrichment in malignant cell nuclei, the genome editing system can induce effective ß-catenin knockout and suppress Wnt/ß-catenin pathway, resulting in notably downregulated proteins involved in tumor progression and immunosuppression. Programmed death-ligand 1 (PD-L1) downregulation in edited tumor cells not only releases the PD-1/PD-L1 brake to improve the cancer killing capability of CD8+ T cells, but also enhances antitumor immune responses of immune cells. This provides a facile strategy to reverse tumor immunosuppression and to restore immunosurveillance and activate anti-tumor immunity.


Subject(s)
Aptamers, Nucleotide/chemistry , B7-H1 Antigen/metabolism , CRISPR-Cas Systems/genetics , Gene Editing/methods , Peptides/chemistry , Animals , Apoptosis , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cell Line, Tumor , Cell Nucleus/metabolism , Humans , Hyaluronic Acid/chemistry , Immunosuppression Therapy , Nanoparticles/chemistry , Oligodeoxyribonucleotides/chemistry , Plasmids/chemistry , Plasmids/metabolism , Programmed Cell Death 1 Receptor/metabolism , beta Catenin/deficiency , beta Catenin/genetics , beta Catenin/metabolism
12.
J Mater Chem B ; 8(16): 3557-3565, 2020 04 29.
Article in English | MEDLINE | ID: mdl-31560346

ABSTRACT

Excessive amounts of Al3+ in the human body can cause adverse effects on immune function and induce several neurodegenerative disorders. So far, most of the reported fluorescent probes for Al3+ present some common drawbacks, such as low sensitivity and poor water solubility. In addition, a number of traditional fluorescent probes failed to image Al3+ in tumor cells due to the lack of tumor cell targeting capacity and cell penetrating abilities. To overcome these shortcomings, we constructed tumor-targeting fluorescent mixed nano-micelles (mPEG-Dye-Biotin) with an average particle size of 21 nm from an amphiphilic polymer containing a Schiff-base fluorescent unit (mPEG-Dye) and another amphiphilic polymer containing a tumor cell recognition ligand (DSPE-PEG-Biotin), through the co-self-assembly of both amphiphilic polymers in water using the film rehydration method. The as-prepared nanoprobe showed a highly sensitive and selective turn-on fluorescence response to Al3+ in aqueous solution with a low detection limit. MTT assay revealed the negligible cytotoxicity of the mPEG-Dye-Biotin nanoprobe to both HeLa cells and COS-7 cells, indicating the safety of mPEG-Dye-Biotin for biological applications. More importantly, the biotinylated nanoprobe showed better ability to enter biotin receptor-positive HeLa cells than that of the non-biotinylated micelle mPEG-Dye, which made it more suitable for imaging Al3+ in biotin receptor-positive tumor cells. This work provides a simple and general strategy to design a highly sensitive and tumor cell-specific metal ion nanoprobe, which can not only be applied in Al3+ imaging, but can also be extended to other ions or biomolecules by changing the incorporated fluorescent unit in the amphiphilic polymer.


Subject(s)
Aluminum/analysis , Biotin/chemistry , Fluorescent Dyes/chemistry , Optical Imaging , Polymers/chemistry , Uterine Cervical Neoplasms/diagnostic imaging , Animals , COS Cells , Chlorocebus aethiops , Female , HeLa Cells , Humans , Hydrogen-Ion Concentration , Ligands , Micelles , Molecular Structure , Particle Size , Schiff Bases/chemistry , Surface Properties
13.
Shanghai Kou Qiang Yi Xue ; 28(1): 41-47, 2019 Feb.
Article in Chinese | MEDLINE | ID: mdl-31080998

ABSTRACT

PURPOSE: The aim of this clinical study was to evaluate the changes of alveolar bone morphology around the upper incisors before and after functional treatment in adolescents using cone-beam CT(CBCT). METHODS: Thirty patients with skeletal Class II mandibular retrusion who were successfully treated with high-pull headgear-activator(HGAC) and Twin-block were selected and divided into 2 groups (HGAC and Twin-block groups), 15 in each group. CBCT was performed before and after treatment, to observe upper incisor movement in the alveolar bone and alveolar bone remodeling. Statistical analysis was performed using SPSS 20.0 software package to analyze the changes of alveolar bone thickness, angle of central incisor and alveolar bone before and after treatment. RESULTS: Horizontally, the edge of the maxillary incisor appeared lingual movement in both groups, while the root apex appeared lingual movement in HGAC group and labial movement in Twin-block group. Vertically, the edge of the maxillary incisor was moved down and the root apex was moved up in all patients, whereas the moving distance was less in the edge and larger in the root apex in HGAC group. The thicknesses of major areas in the alveolar bone significantly increased in HGAC group, while in Twin-block group the labial thickness of the alveolar bone showed significant decrease and the palatal thickness showed significant increase. Moreover, the total thickness of the alveolar bone showed significant increase in both groups, yet Twin-block group showed more increase, and the angle of the alveolar bone showed more decrease in HGAC group. CONCLUSIONS: Both functional appliances can cause positive alveolar bone remodeling in maxillary incisor area. HGAC can achieve a controlled tilt inward movement of the maxillary incisors, intrude the incisors to a certain extent, and allow certain change in the bending angle of the incisor alveolar bone at the same time, which is conducive to improving ClassⅡcraniofacial pattern. Twin-block can tilt the maxillary incisor inward, suggesting that more attention needs to be paid to the control of the torque of the incisor when retracting anterior teeth in fixed orthodontic treatment after Twin-block functional treatment.


Subject(s)
Bone Remodeling , Incisor , Maxilla , Adolescent , Cone-Beam Computed Tomography , Extraoral Traction Appliances , Humans
14.
Mol Pharm ; 16(6): 2616-2625, 2019 06 03.
Article in English | MEDLINE | ID: mdl-31013098

ABSTRACT

To efficiently deliver CpG oligodeoxynucleotides (ODNs) to macrophages for the reversal of cancer-induced immunosuppression, nanoparticles ODN@MCBSA with mannosylated cationic albumin (MCBSA) as a macrophage targeting vector were constructed. Compared with ODN@CBSA with cationic albumin (CBSA) as a vector, ODN@MCBSA exhibited significantly improved cellular uptake mediated by mannose moieties, resulting in significantly enhanced secretion of proflammatory cytokines including IL-12, IL-6, TNF-α, and iNOS. The modulation of macrophages toward the favorable M1 phenotype was confirmed by the upregulated CD80 expression after being treated by ODN delivery systems. In addition to immune cells, the effects of the ODN delivery system on cancerous HeLa cells were also investigated. The results showed that ODN@MCBSA did not affect the overall tumor cell viability. However, enhanced NF-κB, p-Akt, PIK3R3, Fas, and FasL, as well as upregulated caspases were observed in tumor cells, implying the pleiotropic effects on tumor cells. Our study provides a more in-depth understanding on the immunotherapeutic effects of CpG ODNs and highlights the importance of macrophage targeting delivery to minimize the effects on tumor cells. These results indicate that MCBSA could serve as a promising delivery vector of CpG ODNs to macrophages for cancer immunotherapy.


Subject(s)
Macrophages/metabolism , Nanoparticles/chemistry , Oligodeoxyribonucleotides/metabolism , HeLa Cells , Humans , Interleukin-12/metabolism , Interleukin-6/metabolism , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Tumor Necrosis Factor-alpha/metabolism
15.
Colloids Surf B Biointerfaces ; 171: 24-30, 2018 Nov 01.
Article in English | MEDLINE | ID: mdl-30005287

ABSTRACT

Proteins have been extensively explored as versatile nanocarriers for drug delivery due to their complete biocompatibility, ease of surface modification, and lack of toxicity and immunogenicity. In this study, a facile strategy was used to construct aptamer-functionalized albumin-based nanoparticles for effective drug delivery and targeted cancer therapy. A hydrophobic drug, doxorubicin (DOX) was employed to trigger the self-assembly of bovine serum albumin (BSA) to from stable nanoparticles via hydrophobic interaction, and then a tumor targeting aptamer AS1411 was incorporated to the surface of DOX loaded BSA. Due to the specific recognition between AS1411 and its receptor over-expressed on tumor cells, the aptamer-modified nanoparticles show higher cellular uptake and stronger cell inhibitory efficacy against cancerous MCF-7 cells as compared with the nanoparticles without aptamer modification. In addition, DOX loaded aptamer-functionalized nanoparticles can induce more significant down-regulation of Bcl-2 and PCNA as well as up-regulation of pRB, PARP and Bax in MCF-7 cells compared with unmodified nanoparticles, indicating the aptamer modification can induce cell apoptosis more effectively. Besides, aptamer-modified nanoparticles exhibit a significantly improved capability in up-regulating p16, p21 and E-cadherin, and down-regulating EpCAM, vimentin, Snail, MMP-9, CD44 and CD133, implying the favorable effects of drug delivery on the prevention of tumor progression and metastasis.


Subject(s)
Antineoplastic Agents/administration & dosage , Aptamers, Nucleotide/chemistry , Doxorubicin/administration & dosage , Drug Delivery Systems , Nanoparticles/chemistry , Serum Albumin, Bovine/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cattle , Cell Proliferation/drug effects , Doxorubicin/chemistry , Doxorubicin/pharmacology , Drug Carriers/chemistry , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Particle Size , Surface Properties
16.
Biomacromolecules ; 19(7): 2957-2968, 2018 07 09.
Article in English | MEDLINE | ID: mdl-29617556

ABSTRACT

One of critical steps in genome editing by CRISPR-Cas9 is to deliver the CRISPR-Cas9 system into targeted cells. In this study, we developed a dual-targeting delivery system based on polymer/inorganic hybrid nanoparticles to realize highly efficient genome editing in targeted tumor cells as well as in situ detection on the related protein expression in edited cells. The CRISPR-Cas9 plasmid for CDK11 knockout was encapsulated in the core of the delivery system composed of protamine sulfate, calcium carbonate, and calcium phosphate by coprecipitation, and functional derivatives of carboxymethyl chitosan (biotinylated carboxymethyl chitosan with biotin ligands and aptamer-incorporated carboxymethyl chitosan with AS1411 ligands) were decorated on the nanovector surface by electrostatic interactions to form the dual-targeting delivery system. On the basis of the tumor cell targeting capability of biotin and AS1411 ligands as well as the nuclear targeting of AS1411, the dual-targeting system can deliver the CRISPR-Cas9 plasmid into the nuclei of tumor cells to realize highly efficient genome editing, resulting in a dramatic decrease (>90%) in CDK11 protein together with the significant downregulation of other proteins involved in tumor development, including an ∼90% decrease in MMP-9, >40% decrease in VEGF, and ∼70% decrease in survivin. Using the same vector, molecular beacons can be easily delivered to edited cell nuclei to in situ detect the mRNA level of related proteins (p53 and survivin as typical examples) and mRNA distribution in subcellular organelles. Our strategy can realize effective genome editing and in situ detection on related protein expression simultaneously.


Subject(s)
Gene Editing/methods , Gene Silencing , Transfection/methods , Biotin/chemistry , Calcium Carbonate/chemistry , Chitosan/analogs & derivatives , Cyclin-Dependent Kinases/genetics , Cyclin-Dependent Kinases/metabolism , HEK293 Cells , Humans , MCF-7 Cells , Nanoparticles/chemistry , Protamines/chemistry
17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-698484

ABSTRACT

BACKGROUND:Functional graded biomaterials promote the development of human hard tissue replacement.OBJECTIVE:To review the research progress of functional graded biomaterials in human hard tissue replacement.METHODS:The first author retrieved the PubMed and CNKI databases for relevant articles published from January 2010 to April 2017 using the keywords of "functional graded biomaterial,hard tissue replacement implants,preparation methods,performance evaluation,dental implants,osseous tissue" in English and Chinese,respectively.RESULTS AND CONCLUSION:Functional graded biomaterials refer to a kind of heterogeneous composite materials with controllable and programmable gradient properties on account of continuous or quasi-continuous changes in the structure and chemical composition.Hydroxyapatite is the primary choice for the material surface.Serving as an emerging biomaterial,the functional graded biomaterial has unique structure mechanism and excellent properties.It gives full play to the performance advantages of each component and reduces internal stress interface between components.Therefore,the functional graded biomaterial will be an issue of concern in the future because of the optimization of its design,preparation and performance.

18.
ACS Appl Mater Interfaces ; 9(49): 42566-42576, 2017 Dec 13.
Article in English | MEDLINE | ID: mdl-29160061

ABSTRACT

To overcome cancer-associated immunosuppression, we prepared a dual-targeting vector to deliver CpG oligodeoxynucleotides (ODN) to macrophages. The dual-targeting system composed of mannosylated carboxymethyl chitosan (MCMC)/hyaluronan (HA) for macrophage targeting and protamine sulfate for ODN complexation was prepared by self-assembly. The effects of ODN delivery on immune cells was studied in J774A.1 cells. Due to the enhanced delivery efficiency, the dual-targeting delivery system exhibits a higher immune stimulatory activity compared with the monotargeting delivery system containing either MCMC or HA, resulting in a dramatically enhanced secretion of proinflammatory cytokines and a successful shift to activated macrophages (M1). Besides macrophages, the influence of the delivery system on tumor cells (MCF-7) was also investigated. In MCF-7 cells, the increased expressions of nuclear transcription factor-κB (NF-κB), PIK3R3, and phosphorylated protein kinase B (p-Akt) caused by activated NF-κB and phosphoinositide 3-kinase/Akt signalings were observed. Nevertheless, upregulated Fas as well as Fas ligand (FasL) may induce Fas/FasL-mediated apoptosis, which results in the increased expressions of caspases in tumor cells.


Subject(s)
Macrophages , Humans , NF-kappa B , Neoplasms , Oligodeoxyribonucleotides , Phosphatidylinositol 3-Kinases
19.
Environ Sci Pollut Res Int ; 24(25): 20811-20817, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28791528

ABSTRACT

Leachate is a polluting liquid which may cause harmful effects on human health or the environment without a tightly control manner. The leachate management is an important part of the design and operation of bioreactor landfills. To detect the leachate distribution in Laogang Landfill, China, the measurement of electrical resistivity tomography (ERT) was carried out in three areas with different ages. ERT method proved to be an effective non-invasive geophysical method in bioreactor landfills, and the physical properties of waste samples obtained by boreholes were tested in a laboratory. The correlation between the resistivity and the moisture content was described by Archie's law. The result shows that the moisture content of fresh waste is inhomogeneous, while that of aged waste increases with depth. A pseudo 3D model of the moisture content was proposed to improve the understanding of leachate distribution and exhibit the accuracy of the ERT method.


Subject(s)
Environmental Monitoring/methods , Soil Pollutants/analysis , Waste Disposal Facilities , Water Pollutants, Chemical/analysis , Bioreactors , China , Electric Impedance , Environmental Monitoring/instrumentation , Refuse Disposal , Tomography/methods
20.
Chinese Mental Health Journal ; (12): 907-913, 2017.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-703950

ABSTRACT

Objeoctive:To revise and examine the validity and reliability of the Perception of Child Maltreatment Scale (PCMS) in college students.Method:A sample of 555 undergraduates coming from two universities in Harbin and one university in Shanghai was investigated with questionnaire,half of them (n =227) was assessed for exploratory factor analysis and another half of them (n =228) was assessed for confirmatory factor analysis.The criterion validity was tested with the Short Form of Childhood Trauma Questionnaire (CTQ-SF).Totally 57 students were retested for test-retest reliability with 2 week interval.Results:Totally 28 items were retained after exploratory factor analysis,classified into five factors,named psychological abuse,physical abuse,labor,neglect,sexual abuse.And the result of confirmatory factor analysis was that the structure of scale was stable and achieved goodness of fit (x2/df=1.63,CFI =0.912,TLI =0.901,RMSEA =0.048,SRMR =0.059).The scores of psychological abuse,physical abuse and neglect in PCMS were negatively correlated with the scores of psychological abuse,physical abuse and neglect in CTQ-SF respectively (r =0.12-0.15,Ps <0.05).Cronbach's α coefficient of total scale was 0.92,and the Cronbach's α coefficients of subscales were between 0.55 and 0.84.The test-retest reliability were 0.84 for total scale and 0.76-0.91 for five subscales.Conclusion:The validity and reliability of the revised questionnaire is satisfactory,which could be used in the measurement of college students' perception of child maltreatment.

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